Evaluation of Safety and Efficacy of Estetrol in Healthy Men
- Registration Number
- NCT02718378
- Lead Sponsor
- Pantarhei Oncology B.V.
- Brief Summary
The current study is designed as a phase Ib multiple dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of E4 in healthy men after daily oral administration for 28 days.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 45
- Male, age between 40 and 70 years (both inclusive);
- Good physical and mental health as judged by the Investigator determined by medical history, physical examination (including prostate palpation), clinical laboratory, vital signs and ECG recording;
- Body mass index between ≥ 18.5 and ≤ 30.0 kg/m2;
- Normal prostate-specific antigen (PSA) value (< 3.0 ng/mL);
- Non-vasectomized men must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication. Men who have been vasectomized less than 4 months prior to study start must follow the same restrictions as non-vasectomized men;
- Men must agree not to donate sperm from the first dose until 90 days after the last dose;
- Ability to communicate well with the Investigator and to comply with the requirements of the entire study;
- Willing to give informed consent in writing.
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Any clinically significant abnormality following review of medical history, laboratory results, physical examination and ECG at screening as judged by the Investigator;
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Conditions or disorders that might affect the absorption, distribution, metabolism or excretion of any of the study drugs;
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Previous use of steroids within:
- 8 weeks for oral preparations
- 4 weeks for transdermal preparations
- Any time for injections;
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Contraindications for steroids or estetrol;
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Prostate hyperplasia or micturition problems that suggest the presence of prostate hyperplasia;
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Presence of an active acute or chronic infection, including syphilis, HIV or viral hepatitis B and/or C (or previously treated);
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Treatment for any major psychiatric disorder in the previous 12 months or use of antidepressant medication before screening;
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Hypersensitivity to the active substances or to any of the excipients of the investigational product or placebo therapy;
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Use of probiotics (as present in dairy products, fortified foods etc.) during the 3 months before screening and during the clinical study;
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Use of one or more of the following medications:
- Antihypertensive drugs
- Present use or use within 30 days before the start of the study drug of the following drugs: aprepitant, bosentan, armodafinil, phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, glucocorticoids, topiramate, felbamate, rifampicin, clobazamechinacea; vemurafenib, non-nucleoside reverse transcriptase inhibitors, griseofulvin, ketoconazole, and herbal remedies containing Hypericum perforatum
- Any medication (including over-the-counter products) within 14 days before first dosing except for occasional non-steroidal anti-inflammatory drugs (NSAIDs; e.g. ibuprofen); paracetamol is not permitted
- Use of antibiotics;
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Administration of any other investigational drug within 3 months before first dosing;
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Loss of more than 400 mL blood during the 3 months before screening, e.g. as a blood donor, or intention to donate blood in the 3 months after completing the study;
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Subjects with a history of (within 12 months) alcohol or drug abuse or with a positive result at screening, for tests of:
- alcohol intake
- drug abuse;
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Currently smoking or smoked within the last 6 months before screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description estetrol dose level 1 estetrol estetrol given in dose level 1 No added active placebo placebo without estetrol estetrol dose level 2 estetrol estetrol given in dose level 2 estetrol dose level 3 estetrol estetrol given in dose level 3
- Primary Outcome Measures
Name Time Method Number of participants with Adverse Events (AEs) 28 days Changes from baseline measurements considered clinically significant by the Investigator will be reported as AEs.
Change from baseline in hormone levels 28 days The serum concentrations of Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), Estradiol (E2), total testosterone and free testosterone levels (actual values as well as percentage change from pre-dose concentration) will be listed and summarized descriptively by treatment group.
- Secondary Outcome Measures
Name Time Method Change from baseline in glucose levels 28 days The relative change in glucose levels and the actual change from baseline will be calculated by treatment group.
Change from baseline in sex-hormone binding globulin (SHBG) levels 28 days The relative change in SHBG levels and the actual change from baseline will be calculated by treatment group.
Pharmacokinetic effect of estetrol 28 days Peak plasma concentration (Cmax)
Change from baseline in haemostasis parameters 28 days The relative change in Activated Protein C (APC)-resistance, prothrombin factor 1 + 2, D-dimer, free Tissue Factor Pathway Inhibitor (TFPI), antothrombin activity, protein S activity and angiotensinogen levels and the actual change from baseline will be calculated by treatment group.
Change from baseline in lipid parameters 28 days The relative change in total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol, Lipoprotein A (Lp(A)) levels and the actual change from baseline will be calculated by treatment group.
Change from baseline in bone turnover markers 28 days The relative change in osteocalcin, type I collagen telopeptide (CTX-1) and parathyroid hormone (PTH) and the actual change from baseline will be calculated by treatment group.
Trial Locations
- Locations (1)
QPS Netherlands BV
🇳🇱Groningen, Netherlands